TP3, an antimicrobial peptide, inhibits infiltration and motility of glioblastoma cells via modulating the tumor microenvironment

Abstract

Glioblastoma multiforme (GBM) is a cancer of the central nervous system with limited therapeutic outcomes. Infiltrating cancer cells are the contributing factor to high GBM malignancy. The intracranial brain cancer cell infiltration is a complex cascade involving adhesion, migration, and invasion. An arsenal of natural products has been under exploration to overcome GBM malignancy. This study applied the antimicrobial peptide tilapia piscidin 3 (TP3) to GBM8401, U87MG, and T98G cells. The cellular assays and microscopic observations showed that TP3 significantly attenuated cell adhesion, migration, and invasion. A live-cell video clip showed the inhibition of filopodia protrusions and cell attachment. Probing at the molecular levels showed that the proteolytic activities (from secretion), the mRNA and protein expression levels of matrix metalloproteinases-2 and -9 were attenuated. This result strongly evidenced that both invasion and metastasis were inhibited, although metastatic GBM is rare. Furthermore, the protein expression levels of cell-mobilization regulators focal adhesion kinase and paxillin were decreased. Similar effects were observed in small GTPase (RAS), phosphorylated protein kinase B (AKT) and MAP kinases such as extracellular signal-regulated kinases (ERK), JNK, and p38. Overall, TP3 showed promising activities to prevent cell infiltration and metastasis through modulating the tumor microenvironment balance, suggesting that TP3 merits further development for use in GBM treatments. K E Y W O R D Scell mobility, glioblastoma multiforme, infiltration, TP3, tumor microenvironment 3920 | CHEN Et al. 7.2. Prior to the experiments, the TP3 stock solution was protected from light and stored at −20°C.

Sinularin, an Anti-Cancer Agent Causing Mitochondria-Modulated Apoptosis and Cytoskeleton Disruption in Human Hepatocellular Carcinoma

“…The mitochondrial function measurements were modified from the literature [ 34 ]. Oxygen consumption in cells and mitochondria was determined using the Seahorse XF24 Extracellular Flux Analyzer (Seahorse Bioscience, Chicopee, MA, USA).…”

“…The procedure of transwell migration chamber assay was referenced from the publication of Chen et al [ 34 ]. 24-transwell (#3422, BD FalconTM Cell Culture Inserts, BD Biosciences, Bedford, MA, USA) inserts with 8 µm pore size were selected.…”

Pardaxin Activates Excessive Mitophagy and Mitochondria-Mediated Apoptosis in Human Ovarian Cancer by Inducing Reactive Oxygen Species

“…A MTT-based assay was performed to assess cell viability as described in the literature [ 35 ]. A density of 3 × 10 4 cells/well were seeded in transparent 96-well plates (Nunc, Roskilde, Denmark) and placed overnight in a 37 °C incubator equipped with a humidified atmosphere mixing with 5% CO 2 and 95% air.…”

Clinical Applications and Anticancer Effects of Antimicrobial Peptides: From Bench to Bedside

“…ECM can play a crucial role as an anchor to promote cancer cell migration by arranging protein-like focal adhesions (FAs). In other words, TP3 inhibits focal adhesion kinase (FAK), affecting paxillin and reducing FAs ( 134 , 135 ).…”

“…Considering complex intracellular pathways of colorectal cancer cells, AMPs have induced their antineoplastic effects not only by the conventional disrupting cell membrane but also by interfering with critical signalings such as ERK, p38, JNK, and FAK ( 134 , 135 ). Besides, TP4 has shown promising anticancer effects independent of p53 status, making this AMP more appropriate for treating GBM cancer cells with impaired p53 mutations.…”